American journal of respiratory and critical care medicine
-
Am. J. Respir. Crit. Care Med. · Mar 2022
ReviewCystic Fibrosis Transmembrane Conductance Regulator: Roles in Chronic Obstructive Pulmonary Disease.
Chronic obstructive pulmonary disease (COPD) manifests with a variety of clinical presentations, reflecting its complex pathology. Currently, care focuses on symptom amelioration and prevention of complications and thus is generally tailored to disease severity rather than targeting specific pathophysiologic mechanisms. Chronic inflammation and mucus hypersecretion are key features of COPD. ⋯ Recent evidence suggests considerable similarities between COPD and cystic fibrosis (CF), a disease in which chloride ion channel dysfunction has been extensively studied (in particular CFTR [CF transmembrane conductance regulator]). Understanding commonalities between CF and COPD, and the role of CFTR in CF, may help in designing strategies targeting ion channel dysfunction and lead to new treatments with potential to alter the natural history of disease progression. Here, we review the roles of airway mucus and CFTR in normal lung function, the previously underestimated contribution of mucus stasis to the development of COPD, and the evidence for targeting CFTR to counteract mucus accumulation.
-
Am. J. Respir. Crit. Care Med. · Mar 2022
Randomized Controlled TrialLong-Term Safety and Efficacy of Tocilizumab in Early Systemic Sclerosis-Interstitial Lung Disease: Open Label Extension of a Phase 3 Randomized Controlled Trial.
Rationale: Tocilizumab, an anti-IL-6 receptor antibody, had no statistically significant effect on skin sclerosis but preserved lung function over 48 weeks in patients with early systemic sclerosis (SSc)-associated interstitial lung disease (ILD) in a phase 3 randomized controlled trial. Objectives: Assess long-term safety and efficacy of tocilizumab. Methods: Adults with diffuse cutaneous SSc for ⩽60 months and elevated acute-phase reactants, including those with ILD, received weekly placebo or tocilizumab 162 mg subcutaneously in the 48-week, double-blind period and then open-label tocilizumab from Weeks 48 to 96 (placebo-tocilizumab; continuous-tocilizumab). ⋯ Conclusions: Tocilizumab preserved lung function, slowing decline in FVC, in patients with SSc, including those with ILD. Long-term safety was consistent with the known safety profile of tocilizumab. Clinical trial registered with www.clinicaltrials.gov (NCT02453256).
-
Am. J. Respir. Crit. Care Med. · Mar 2022
Race/Ethnicity, Spirometry Reference Equations and Prediction of Incident Clinical Events: The Multi-Ethnic Study of Atherosclerosis (MESA) Lung Study.
Rationale: Normal values for FEV1 and FVC are currently calculated using cross-sectional reference equations that include terms for race/ethnicity, an approach that may reinforce disparities and is of unclear clinical benefit. Objectives: To determine whether race/ethnicity-based spirometry reference equations improve the prediction of incident chronic lower respiratory disease (CLRD) events and mortality compared with race/ethnicity-neutral equations. Methods: The MESA Lung Study, a population-based, prospective cohort study of White, Black, Hispanic, and Asian adults, performed standardized spirometry from 2004 to 2006. ⋯ Findings were similar for mortality (difference in C statistics for FEV1, -0.002; 95% CI, -0.008 to 0.003; difference in C statistics for FVC, -0.004; 95% CI, -0.009 to 0.001). Conclusions: There was no evidence that race/ethnicity-based spirometry reference equations improved the prediction of clinical events compared with race/ethnicity-neutral equations. The inclusion of race/ethnicity in spirometry reference equations should be reconsidered.
-
Am. J. Respir. Crit. Care Med. · Mar 2022
Randomized Controlled TrialEffect of Weight Loss and CPAP on OSA and Metabolic Profile Stratified by Craniofacial Phenotype: A Randomized Clinical Trial.
Rationale: Craniofacial structure is believed to modulate the effect of weight loss on obstructive sleep apnea (OSA), but whether this affects metabolic profile after weight loss compared with continuous positive airway pressure (CPAP) is unknown among obese Chinese patients with OSA. Objectives: To compare the change in metabolic profile between a lifestyle modification program (LMP), stratified by craniofacial phenotype, and CPAP therapy for 6 months. Methods: We randomly assigned 194 patients with body mass index ⩾ 25 kg/m2 and moderate to severe OSA to participate in the LMP or receive CPAP therapy for 6 months in a 2:1 ratio. ⋯ There was no significant difference in hsCRP (median [interquartile range], -0.7 [-1.3 to 0.1] vs. -0.7 [-1.5 to -0.2] mg/L; P = 0.884) and insulin sensitivity (median [interquartile range], 0.5 [-0.2 to 1.9] vs. 0.6 [0.1 to 2.0]; P = 0.4860) between the LMP-small MMV and LMP-large MMV groups. Conclusions: Weight reduction alleviated subclinical inflammation and improved insulin sensitivity more than CPAP among obese Chinese patients with moderate to severe OSA, and this effect was not influenced by craniofacial structure. Clinical trial registered with www.clinicaltrials.gov (NCT03287973).
-
Am. J. Respir. Crit. Care Med. · Mar 2022
Long-Term Air Pollution Exposure and COVID-19 Mortality: A Patient-Level Analysis from New York City.
Rationale: Risk factors for coronavirus disease (COVID-19) mortality may include environmental exposures such as air pollution. Objectives: To determine whether, among adults hospitalized with PCR-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), long-term air pollution exposure is associated with the risk of mortality, ICU admission, or intubation. Methods: We performed a retrospective analysis of SARS-CoV-2 PCR-positive patients admitted to seven New York City hospitals from March 8, 2020, to August 30, 2020. ⋯ In multivariable models, a higher level of long-term exposure to PM2.5 was associated with an increased risk of mortality (risk ratio, 1.11 [95% confidence interval, 1.02-1.21] per 1-μg/m3 increase in PM2.5) and ICU admission (risk ratio, 1.13 [95% confidence interval, 1.00-1.28] per 1-μg/m3 increase in PM2.5). In multivariable models, neither NO2 nor BC exposure was associated with COVID-19 mortality, ICU admission, or intubation. Conclusions: Among patients hospitalized with COVID-19, a higher long-term PM2.5 exposure level was associated with an increased risk of mortality and ICU admission.